The primary goal of this project is to determine the role of variation in HIV sequences in causing the various clinical manifestations seen in AIDS. In vivo env sequence analysis of viruses associated with dementia suggested that unique viral strains may be responsible for the occurrence of HIV dementia. In contrast, other analyses indicated that dementia was not associated with higher levels of viral DNA. The influence of the V3 region of the envelope gene on macrophage tropism and the NSI and SI phenotypes was mapped to individual V3 amino acids, and it was found that usually macrophage tropism and the SI phenotype were independently determined by amino acids at different V3 positions. This finding provides an explanation for the occurrence of HIV strains which exhibit both the SI phenotype and macrophage tropism. More recently infectious HIV molecular clones with mutations in and near the V3 region were studied for their utilization of specific coreceptors and for their behavior in SCID /HuPBL mice